The broad objective of this project is to study the macrophage (M phi) cell membrane, which may be a critical structure for the understanding of the way in which M phis discriminate and kill foreign cells, for understanding their regulatory interactins with lymphocytes and the way in which immunomodulators affect them. Our hypothesis is that changes of the membrane will reflect the functional state of the M phi. The goals will be: 1) to provide additional insight into the protein composition of the macrophage membrane; and 2) to analyze the possible involvement of these molecules during immunologically important events, such as the recognition and/or killing of tumor cells by tumoricidal M phis. Membrane proteins will be radiolabeled directly with surface specific methods such as radioiodination and tritiation of sialic acid residues of glycoproteins, or by biosynthetic labeling during in vitro culture of these cells. Special emphasis is placed on the preservation of the biological properties of the M phis, including viability, phagocytosis and tumor cytotoxicity. The radioactive membrane components can then be analyzed by a combination of biochemical techniques, in particular gel electrophoresis of proteins. Identification and characterization of membrane proteins from M phis "activated" to different degrees in vivo or in vitro may provide insight into the functional contribution of such components in the immune responses of these cells.